Trifluoroacetic acid methylene chloride → 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-2-fluoro-5-methoxy-N-piperidin-4-yl-benzamide

HRID 1676710Notes

Reaction equation

HRID 1676710 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15](=[O:46])[C:16]2[CH:21]=[C:20]([O:22][CH3:23])[C:19]([NH:24][C:25]3[N:26]=[CH:27][C:28]4[N:34]([CH3:35])[C:33](=[O:36])[C:32]([F:38])([F:37])[CH2:31][N:30]([CH:39]5[CH2:43][CH2:42][CH2:41][CH2:40]5)[C:29]=4[N:44]=3)=[CH:18][C:17]=2[F:45])[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O.ClCCl>ClCCl>[CH:39]1([N:30]2[CH2:31][C:32]([F:38])([F:37])[C:33](=[O:36])[N:34]([CH3:35])[C:28]3[CH:27]=[N:26][C:25]([NH:24][C:19]4[C:20]([O:22][CH3:23])=[CH:21][C:16]([C:15]([NH:14][CH:11]5[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]5)=[O:46])=[C:17]([F:45])[CH:18]=4)=[N:44][C:29]2=3)[CH2:40][CH2:41][CH2:42][CH2:43]1

Participants

4

Reactant 2

HCID 21863450Trifluoroacetic acid methylene chlorideHCID 579556014-[4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido [4,5-b][1,4]diazepin-2-ylamino)-2-fluoro-5-methoxy-benzoyl-amino]-piperidin-1-carboxylic acid tert-butyl ester

Product 1

HCID 579556724-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-2-fluoro-5-methoxy-N-piperidin-4-yl-benzamideYield 83%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 0.071 g (0.11 mmole) of 4-[4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-2-fluoro-5-methoxy-benzoyl-amino]-piperidin-1-carboxylic acid tert-butyl ester (I-177) and 3 mL of dichloromethane was added 6 mL of trifluoroacetic acid-dichloromethane (1:1). The mixture was stirred at room temperature for 18 hours, and then concentrated under reduced pressure. The residue was diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate solution, then brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with methanol-dichloromethane (gradient, 0:100-25:75) to give 0.050 g of 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-2-fluoro-5-methoxy-N-piperidin-4-yl-benzamide (I-178).

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionThe residue was diluted with ethyl acetate
  3. washwashed with saturated aqueous sodium bicarbonate solution
  4. dry with materialbrine, dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with methanol-dichloromethane (gradient, 0:100-25:75)

Sources & evidence

ORD record
ord-e679f57831c94ecbb7aa2bb514f60804
Source dataset
uspto-grants-2011_08
Patent number
US08003785B2

Reaction notes

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